PRIORITY RESEARCH PAPER

AGING, Vol 1, No 11 , pp 903-936
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Drosophila melanogaster p53 has developmental stage-specific and sex-specific effects on adult life span indicative of sexual antagonistic pleiotropy

Morris Waskar1,6, Gary N. Landis1, Jie Shen1, Christina Curtis1,2, Kevin Tozer1, Diana Abdueva1,3, Dmitriy Skvortsov1,4, Simon Tavaré1,2 , and John Tower1
1 Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA
2 Department of Oncology, University of Cambridge Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way Cambridge CB2 0RE, England
3 Current address: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9034, USA
4 Current address: Department of Human Genetics, UCLA School of Medicine, University of California, Los Angeles, USA
6 Current address: Unilever Research Center, Bangalore 560066, India
Running title:
p53 sexual antagonistic pleiotropy
Key words:
aging, sexual conflict, Geneswitch, maternal effects, tumor suppressor
Received:
09/24/09; accepted: 10/26/09; published on line: 10/27/09
Correspondence:
E-mail:

Abstract

Truncated and mutant forms ofp53 affect life span in Drosophila, nematodes and mice, however the role of wild-type p53 in aging remains unclear. Here conditional over-expression of both wild-type and mutant p53 transgenes indicated that, in adult flies, p53 limits life span in females but favors life span in males. In contrast, during larval development, moderate over-expression of p53 produced both male and female adults with increased life span. Mutations of the endogenous p53 gene also had sex-specific effects on life span under control and stress conditions: null mutation of p53 increased life span in females, and had smaller, more variable effects in males. These developmental stage-specific and sex-specific effects of p53 on adult life span are consistent with a sexual antagonistic pleiotropy model.